JPH0196158A - Anti-inflammatory agent - Google Patents
Anti-inflammatory agentInfo
- Publication number
- JPH0196158A JPH0196158A JP62255699A JP25569987A JPH0196158A JP H0196158 A JPH0196158 A JP H0196158A JP 62255699 A JP62255699 A JP 62255699A JP 25569987 A JP25569987 A JP 25569987A JP H0196158 A JPH0196158 A JP H0196158A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- unsaturated bond
- compound expressed
- inflammatory
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 229940121363 anti-inflammatory agent Drugs 0.000 title claims abstract description 8
- 239000002260 anti-inflammatory agent Substances 0.000 title claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 26
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 6
- 150000003839 salts Chemical class 0.000 claims abstract description 6
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 239000002075 main ingredient Substances 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 2
- 230000002496 gastric effect Effects 0.000 abstract description 12
- 230000000694 effects Effects 0.000 abstract description 11
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 8
- 125000002843 carboxylic acid group Chemical group 0.000 abstract description 6
- -1 Oleyl ester Chemical class 0.000 abstract description 4
- 229960001259 diclofenac Drugs 0.000 abstract description 4
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 abstract description 4
- 229960001193 diclofenac sodium Drugs 0.000 abstract description 4
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 abstract description 4
- 125000005907 alkyl ester group Chemical group 0.000 abstract description 3
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 150000002367 halogens Chemical class 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 239000003814 drug Substances 0.000 description 14
- 229940079593 drug Drugs 0.000 description 13
- 238000012360 testing method Methods 0.000 description 9
- 239000000203 mixture Substances 0.000 description 5
- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000000679 carrageenan Substances 0.000 description 2
- 229920001525 carrageenan Polymers 0.000 description 2
- 235000010418 carrageenan Nutrition 0.000 description 2
- 229940113118 carrageenan Drugs 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 210000002683 foot Anatomy 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 210000001156 gastric mucosa Anatomy 0.000 description 2
- 229940057995 liquid paraffin Drugs 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- BORJONZPSTVSFP-UHFFFAOYSA-N tetradecyl 2-hydroxypropanoate Chemical compound CCCCCCCCCCCCCCOC(=O)C(C)O BORJONZPSTVSFP-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 2
- IFABLCIRROMTAN-MDZDMXLPSA-N (e)-1-chlorooctadec-9-ene Chemical compound CCCCCCCC\C=C\CCCCCCCCCl IFABLCIRROMTAN-MDZDMXLPSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 244000175448 Citrus madurensis Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 235000017317 Fortunella Nutrition 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N alpha-methyl toluene Natural products CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 238000011549 displacement method Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 108010027678 lagenin Proteins 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 150000003017 phosphorus Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
「産業上の利用分野」
本発明は抗炎症剤として有用な化合物を提供するもので
ある。DETAILED DESCRIPTION OF THE INVENTION "Industrial Application Field" The present invention provides compounds useful as anti-inflammatory agents.
「従来技術」
抗炎症剤の研究は古くからなされ、数多くの化合物が合
成てれてきた。その内でも式［１１）で表わ冨れる化合
物のナトリクム塩はジクロフェナ、クナトリクムの一般
名で知られ、医療の場で広く用いられており、その誘導
体についても種々検討されている。``Prior Art'' Research on anti-inflammatory agents has been conducted for a long time, and many compounds have been synthesized. Among them, the sodium salt of the compound represented by formula [11] is known by the common names of diclofena and cunatrichum, and is widely used in medical fields, and various derivatives thereof have also been studied.
「発明が解決しようとする問題点および問題を解決する
為の手段」
抗炎症剤は大きく分けるとステロイドと非ステ性
ロイド性に分けられる。非ステロイド抗炎症剤はへ
カルボン酸基を有するものが主体である。一般にカルボ
ン酸基を有する抗炎症剤は胃粘膜障害が強く２代表的な
副作用とされてｂる。その副作用を軽減する為、カルボ
ン酸基をエステル等の誘導体にする事が研究されている
。ジクロフェナックナトリウムは抗炎症作用が強く、シ
かも従来の非ステロイド性抗炎症剤にくらべて胃粘膜障
害が少ない利点がある。しかしながら、その胃粘膜障害
はまだ充分軽減されたとはいえず、さらにその軽減をは
かる必要があった。カルボン酸基をエステル化すると胃
粘膜障害が軽減されるとされているが。``Problems to be solved by the invention and means for solving them'' Anti-inflammatory agents can be broadly divided into steroids and non-steroids. Non-steroidal anti-inflammatory drugs mainly have a hecarboxylic acid group. Generally, anti-inflammatory agents having a carboxylic acid group cause gastric mucosal damage, which is considered to be a major side effect. In order to reduce the side effects, research is being conducted on converting the carboxylic acid group into a derivative such as an ester. Diclofenac sodium has a strong anti-inflammatory effect and has the advantage of causing less gastric mucosal damage than conventional non-steroidal anti-inflammatory drugs. However, it cannot be said that the gastric mucosal damage has been sufficiently alleviated, and there is a need to further reduce the damage. It is said that esterifying the carboxylic acid group reduces gastric mucosal damage.
重要な事はその抗炎症効果を減少させることなく胃粘膜
障害を軽減させることにある。本発明者らは種々の化合
物を検討した結果、不飽和結合を一個有する高級アルキ
ルエステルとする事により。The important point is to alleviate gastric mucosal damage without reducing its anti-inflammatory effect. The present inventors studied various compounds and decided to use a higher alkyl ester having one unsaturated bond.
それらの問題が一挙に解決できることを見い出した。I discovered that all of these problems could be solved all at once.
「発明の開示」
本発明は一般式ＣＩ）で表わされる化合物およびその塩
類、並びにそれらを主成分とする抗炎症剤に関する。"Disclosure of the Invention" The present invention relates to compounds represented by the general formula CI), salts thereof, and anti-inflammatory agents containing them as main ingredients.
上記で規足した基をさらに詳しく説明すると。 Let me explain the groups defined above in more detail.
ハロゲン原子とはフッ素、塩素ま九は臭素を示し。Halogen atom means fluorine, and chlorine means bromine.
高級アルキル基とは直鎖または分枝の１０〜３０個の炭
素原子を有するアルキル基を示す。また不飽和結合の位
置については特に限定はなく、さらに立体異性体も本発
明に包含される。Higher alkyl group refers to a straight-chain or branched alkyl group having 10 to 30 carbon atoms. Furthermore, there is no particular limitation on the position of the unsaturated bond, and stereoisomers are also included in the present invention.
カルボン酸基を有する非ステロイド性抗炎症剤の代表的
な副作用として胃粘膜障害がある。この副作用を軽減す
る為にカルボン酸基をエステル等の訪導体に導く検討が
種々なされてきた。しかしながら、最も重要な事は抗炎
症効果を減少嘔せずに胃粘膜障害を軽減させる事にある
。末完り」者らは種々の化合物を鋭意研究した結果、不
飽和結合Ｔｈ−（ｆｉｌ含む高級アルキルエステルがこ
の条件を満足し得るものである！Ｊ！を見い出した。本
発明化合物の代表例としてジクロフェナックのオレイル
エステルの効果を後述の薬理試験例の項に詳細に記載す
る。Gastric mucosal damage is a typical side effect of non-steroidal anti-inflammatory drugs having a carboxylic acid group. In order to alleviate this side effect, various studies have been made to introduce the carboxylic acid group into a conductor such as ester. However, the most important thing is to alleviate gastric mucosal damage without reducing the anti-inflammatory effect. As a result of intensive research on various compounds, the researchers found that higher alkyl esters containing an unsaturated bond Th-(fil can satisfy this condition!J!).Representative examples of compounds of the present invention The effects of oleyl ester of diclofenac are described in detail in the pharmacological test examples section below.
本発明化合物は経口または局所（点眼、経皮等）投与す
る事ができ、投与量は年令、性別、剤屋等によって異な
るが１通常１ｇ９〜１，０００ ！を１日１回または数
回に分けて投与する事ができる。The compound of the present invention can be administered orally or locally (eye drops, transdermally, etc.), and the dosage varies depending on age, gender, pharmacist, etc., but it is usually 1g9 to 1,000! It can be administered once a day or in several divided doses.
本発明化合物の塩としては医薬として許容される塩酸塩
、硫酸塩、リン敵塩、フマル酸塩、マレイン酸塩、コハ
クば塩、シュウ酸塩等が例示される。Examples of the salts of the compounds of the present invention include pharmaceutically acceptable hydrochlorides, sulfates, phosphorus salts, fumarates, maleates, succinic salts, oxalates, and the like.
以下、薬理試験例および実施例で石らに詳しく説明する
。A detailed explanation will be given below using pharmacological test examples and examples.
薬理試験例
１）抗炎症効果
本発明化合物の抗炎症作用をラットカラゲニン足浮皿モ
デルを用いて検討した。Pharmacological Test Example 1) Anti-inflammatory effect The anti-inflammatory effect of the compound of the present invention was investigated using a rat carrageenan foot floating dish model.
被験薬物Ｖｉ実施例１で合成嘔九だジクロフェナックの
オレイルエステル（式〔■〕）を用論。In Example 1 of the test drug Vi, oleyl ester (formula [■]) of the synthetic drug diclofenac was used.
比較薬物としてジクロフェナックナトリウム金柑いた。Diclofenac sodium kumquat was used as a comparison drug.
方法
Ｗｉａｔａｒ系雄性ラット（−酵五匹）を体′Ｘｆｉが
ほぼ等しくなる様に郭公けし、１％カラゲニン溶液０．
１ ｄを右後肢足し皮下に注射することにより足浮ｎを
惹起した。右後肢の容積は、水置換法により１％カラゲ
ニン注射前、注射後０．５，１，２，３゜４および５時
間目に測定した。Method Male Wiatar rats (5 rats) were placed in a cage so that their bodies'
Paw floatation was induced by subcutaneously injecting 1 d into the right hind leg. The volume of the right hind paw was measured by the water displacement method before injection of 1% carrageenan and at 0.5, 1, 2, 3° 4 and 5 hours after injection.
被験薬物および比較薬物はいずれも０．５ ％Ｔｗｅｅ
ｎ溶
８０液に懸濁あるいは溶解し、各々３〜／ Ｋｑおよへ
び１０′Ｉ９／Ｋｇの量で１チ力ラゲニン注射１時間前
に経口投与し九。Both the test drug and comparison drug were 0.5% Twee.
The drug was suspended or dissolved in a solution of 3 to 10 kg and administered orally at an amount of 3 to 10 kg per kg, respectively, 1 hour before injection of 100 mg of lagenin.
結果 ＥＤ３．値を４時間目の浮腫抑制率より算出した。result ED3. The value was calculated from the edema suppression rate at 4 hours.
被験薬物および比較薬物のＥ Ｉ）３０値（■／Ｋｇ）
はそれぞれ７．６および５．５でほぼ同程度の値を示し
９両者の抗炎症作用に差がない事がわかった。E I) 30 value of test drug and comparative drug (■/Kg)
The values were 7.6 and 5.5, respectively, which were almost the same.9 It was found that there was no difference in the anti-inflammatory effects of the two.
２）胃粘膜に及ぼす影響 本発明化合物の胃粘膜に及ぼす影響を調べた。2) Effect on gastric mucosa The effects of the compounds of the present invention on gastric mucosa were investigated.
被験薬物および比較薬物は前記と同じ。The test drug and comparative drug were the same as above.
方法
２４時間絶食させた雄性Ｗｉａｔａｒ系ラット（−群へ
匹）に被験薬物および比較薬物を０．５％Ｔｗｅｅｎ８
０溶液に懸濁あるいは靜解し、０．５〜８０町／ Ｋｙ
の量で投与した。Method Male Wiatar rats (group -) were fasted for 24 hours and treated with 0.5% Tween8.
Suspended or dissolved in 0 solution, 0.5 to 80 towns/Ky
was administered in an amount of
胃粘膜障害発生をａｌｌ ｏｒ ｎｏｎｅの判定で行な
い５０％胃粘膜障害用量（ＵＤ５Ｑ値）を算出した。The occurrence of gastric mucosal damage was judged as all or none, and the 50% gastric mucosal damage dose (UD5Q value) was calculated.
結果
被験薬物および比較薬物のＵ Ｉ）５ｏ値（’ｆ／Ｋｇ
）はそれぞ扛５５．５および１２．３であり、被験薬物
の胃粘膜障害は比較薬物にくらべてけるかに弱く。Results U I) 5o value ('f/Kg) of test drug and comparative drug
) were 55.5 and 12.3, respectively, and the gastric mucosal damage caused by the test drug was much weaker than that of the comparative drug.
不発「１化合物の優れた効果を証り１している。Unexploded ``1'' proves the excellent effects of the compound.
「実施例」
実施例１
ジクロフェナックのオレイルエステルの製造オレイルク
ロリド（５，２ｙ）、ジクロフェナックナトリウム（４
，８ｙ）およびヨウ化ナトリウム（２，７ｙ） ｔＤＭ
Ｆ （６０ｄ） ｌＩＣ７Ｊｎえ１時間１００℃附近で
撹拌した。放冷後２反応液に酢酸エチルとベンゼンの混
液を加え、水、飽和食塩水で洗浄後無水硫酸す） ＩＪ
クムで乾燥した。溶媒を減圧留去後、シリカゲルカラム
クロマトで精製し、標記化合物７．９りを油状物として
得た。"Example" Example 1 Production of oleyl ester of diclofenac Oleyl chloride (5,2y), diclofenac sodium (4
,8y) and sodium iodide (2,7y) tDM
F (60d) IC7Jn and stirred at around 100°C for 1 hour. After cooling, add a mixture of ethyl acetate and benzene to the two reaction solutions, wash with water and saturated saline, and add anhydrous sulfuric acid)
Dry with cum. After distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography to obtain 7.9 g of the title compound as an oil.
ＩＲ（ｎｅａｔ、（！ｌｌｌ−１）：３３２０．２９２
０，２８５２゜１７１９．１５０４．１４５１．１２９
１．１１４６゜ＮＭＲ（ＣＤＣｌ３ 、δ） ： ０．
８７ （３Ｈ、ｂｒ ｔ 、 Ｃ１（３） 。IR(neat, (!llll-1):3320.292
0,2852°1719.1504.1451.129
1.1146°NMR (CDCl3, δ): 0.
87 (3H, br t, C1(3).
１．０５〜２．２５（２９Ｈ，ｍ、 ＣＬ１２−およ
びＮＨ）、３−７７（２Ｂ、ｓ、 ＣＨ２ＣＯＯ）。1.05-2.25 (29H, m, CL12- and NH), 3-77 (2B, s, CH2COO).
４．１０ （２Ｈ、ｔ 、 Ｊ”６Ｈｚ 、 ＣＯ２
すし） 。4.10 (2H, t, J”6Hz, CO2
sushi).
５．２０〜５．４２ （２Ｈ、ｍ 、 −ＣＨ＝ＣＨ−
） 。5.20-5.42 (2H, m, -CH=CH-
).
６．４８ （ＩＨ、ｄ−ｄ 、 Ｊ＝７ 、２Ｈｚ 、
アロマティクＨ） 、 ６．７２〜７．４８ （６Ｈ、
ｍ 、アＯｆティクＨ）実施例２
本発明化合物の製剤例を示す。6.48 (IH, dd, J=7, 2Hz,
Aromatic H), 6.72-7.48 (6H,
Example 2 A formulation example of the compound of the present invention is shown.
１）錠剤
処方
本発明化合物 ３０Ｔｎｇ＠質無水ケイ
ｆｆ１ ４０■結晶セルロース
６０キ
ヒドロキシプロビルセルロース ８■計１４
２１１！ｊ！１
製法
本発明化合物をできるだけ少量のエタノールに溶解した
後、軽質無水ケイ酸を加えて十分に混合する。この粉末
を４０〜５０°Ｃで乾燥後。1) Tablet formulation Compound of the present invention 30 Tng @ quality anhydrous silicon ff1 40 ■ Crystalline cellulose
60-hydroxypropyl cellulose 8 ■ Total 14
211! j! 1 Production method After dissolving the compound of the present invention in as little amount of ethanol as possible, light silicic anhydride is added and thoroughly mixed. After drying this powder at 40-50°C.
結晶セルロース、ヒドロキシグロビルセルロース、ステ
アリン酸マグネシウムと混合し、圧縮成形して錠剤をイ
ひる。Mix with crystalline cellulose, hydroxyglobil cellulose, and magnesium stearate and compress to form tablets.
なお１本錠剤は通常のフィルムコーティングを行っても
よく、さらに糖衣を行うこともできる。In addition, one tablet may be coated with a usual film or may be further coated with sugar.
２）軟膏
処方
本発明化合物 １ｙ
乳酸ミリスチル ５ｙ
イソステアリン酸 １５ｙ
バラオキシ安息香酸ブチル ０．０２ｙ流動パ
ラフイン １０ｙ
製法
乳酸ミリスチル、イソステアリン酸、バラオキシ安息香
酸ブチル、白色ワセリンを９０℃で混合し均一な溶液と
する。６０〜７０℃に冷却後、流動パラフィンに溶解し
た本発明化合物を刀口える。十分に撹拌した後、室温せ
で冷却する。2) Ointment formulation Compound of the present invention 1y Myristyl lactate 5y Isostearic acid 15y Butyl roseoxybenzoate 0.02y Liquid paraffin 10y Production method Mix myristyl lactate, isostearic acid, butyl roseoxybenzoate, and white petrolatum at 90°C to make a uniform solution. After cooling to 60 to 70°C, the compound of the present invention dissolved in liquid paraffin is poured. After thorough stirring, cool to room temperature.
なお必要ならば冷却前にろ過を行なう。If necessary, filter before cooling.
「発明の効果」
本発明化合物は抗炎症効果を減少させずに、胃粘膜障害
を軽減させるという従来化合物にはみられなかったすぐ
れた効果を示すものである。"Effect of the Invention" The compound of the present invention exhibits an excellent effect that has not been seen in conventional compounds, in that it alleviates gastric mucosal damage without reducing its anti-inflammatory effect.
Claims (2)
類。 ▲数式、化学式、表等があります▼〔 I 〕 〔式中、ＸおよびＸ′は同一かまたは異なつたハロゲン
原子を示す。Ｒは不飽和結合を一個含む高級アルキル基
を示す。〕(1) Compounds represented by general formula [I] and salts thereof. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [I] [In the formula, X and X' represent the same or different halogen atoms. R represents a higher alkyl group containing one unsaturated bond. ]
類を主成分とする抗炎症剤。 ▲数式、化学式、表等があります▼〔 I 〕 〔式中、ＸおよびＸ′は同一かまたは異なつたハロゲン
原子を示す。Ｒは不飽和結合を一個含む高級アルキル基
を示す。〕(2) An anti-inflammatory agent whose main ingredient is a compound represented by the general formula [I] or a salt thereof. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [I] [In the formula, X and X' represent the same or different halogen atoms. R represents a higher alkyl group containing one unsaturated bond. ]
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62255699A JPH0196158A (en) | 1987-10-09 | 1987-10-09 | Anti-inflammatory agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62255699A JPH0196158A (en) | 1987-10-09 | 1987-10-09 | Anti-inflammatory agent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0196158A true JPH0196158A (en) | 1989-04-14 |
Family
ID=17282409
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62255699A Pending JPH0196158A (en) | 1987-10-09 | 1987-10-09 | Anti-inflammatory agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0196158A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001522351A (en) * | 1997-01-24 | 2001-11-13 | ノルスク・ヒドロ・アーエスアー | New fatty acid derivatives |
| WO2009037705A2 (en) * | 2007-09-20 | 2009-03-26 | Ramot At Tel Aviv University Ltd. | Esters of n-phenylanthranilic acid for use in the treatment of cancer and inflammation |
| US8278357B2 (en) | 2002-10-21 | 2012-10-02 | Ramot At Tel-Aviv University Ltd. | Derivatives of N-phenylanthranilic acid and 2-benzimidazolone as potassium channel and/or neuron activity modulators |
| US8765815B2 (en) | 2007-09-20 | 2014-07-01 | Ramot At Tel-Aviv University Ltd. | N-phenyl anthranilic acid derivatives and uses thereof |
-
1987
- 1987-10-09 JP JP62255699A patent/JPH0196158A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001522351A (en) * | 1997-01-24 | 2001-11-13 | ノルスク・ヒドロ・アーエスアー | New fatty acid derivatives |
| JP4698773B2 (en) * | 1997-01-24 | 2011-06-08 | クラヴィス・ファルマ・アーエスアー | Novel fatty acid derivatives |
| US8278357B2 (en) | 2002-10-21 | 2012-10-02 | Ramot At Tel-Aviv University Ltd. | Derivatives of N-phenylanthranilic acid and 2-benzimidazolone as potassium channel and/or neuron activity modulators |
| US8618169B2 (en) | 2002-10-21 | 2013-12-31 | Ramot At Tel-Aviv University Ltd. | Derivatives of N-phenylanthranilic acid and 2-benzimidazolone as potassium channel and/or neuron activity modulators |
| WO2009037705A2 (en) * | 2007-09-20 | 2009-03-26 | Ramot At Tel Aviv University Ltd. | Esters of n-phenylanthranilic acid for use in the treatment of cancer and inflammation |
| WO2009037705A3 (en) * | 2007-09-20 | 2009-07-09 | Univ Ramot | Esters of n-phenylanthranilic acid for use in the treatment of cancer and inflammation |
| US8765815B2 (en) | 2007-09-20 | 2014-07-01 | Ramot At Tel-Aviv University Ltd. | N-phenyl anthranilic acid derivatives and uses thereof |
| US9403756B2 (en) | 2007-09-20 | 2016-08-02 | Ramot At Tel-Aviv University Ltd. | N-phenyl anthranilic acid derivatives and uses thereof |
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